cp-675,206 (ctla4-blocking monoclonal antibody) combined with dendritic cell vaccine therapy in treating patients with stage iii or stage iv melanoma that cannot be removed with surgery

Conditions: Melanoma (Skin)

Summary: rationale: biological therapies, such as cp-675,206, work in different ways to stimulate the immune system and stop tumor cells from growing. vaccines may make the body build an immune response to kill tumor cells. combining cp-675,206 with vaccine therapy may cause a stronger immune response and kill more tumor cells. purpose: this phase i trial is studying the side effects and best dose of cp-675,206 when given with vaccine therapy in treating patients with stage iii or stage iv melanoma that cannot be removed with surgery.

objectives: primary * determine the safety and maximum tolerated dose of anti-cytotoxic t-lymphocyte-associated antigen-4 monoclonal antibody (ctla4-blocking monoclonal antibody; cp-675,206) administered with autologous dendritic cells pulsed with mart-1 antigen in patients with unresectable stage iii or stage iv melanoma. * determine the biological activity and immune effects of this regimen in these patients. secondary * correlate ctla4 genotype with safety of this regimen and/or immune response in these patients. * determine, preliminarily, the efficacy of this regimen, in terms of clinical benefit rate, in these patients. outline: this is an open-label, dose-escalation study of anti-cytotoxic t-lymphocyte-associated antigen-4 monoclonal antibody (ctla4-blocking monoclonal antibody; cp-675,206). patients receive cp-675,206 iv on days 0, 28, 60, and 90 and autologous dendritic cells pulsed with mart-1 antigen intradermally on days 0, 14, and 28. after day 120, patients with stable or responding disease may receive additional doses of cp-675,206 monthly in the absence of disease progression or unacceptable toxicity cohorts of 3-6 patients receive escalating doses of cp-675,206 until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. patients are followed every 3 months. projected accrual: a total of 3-21 patients will be accrued for this study within 3-10 months.

Eligibility criteria:
inclusion criteria: * histologically confirmed cutaneous or mucosal melanoma, meeting criteria for 1 of the following: * unresectable stage iii disease (locally relapsed unresectable, in-transit lesions, or unresectable draining nodes) * stage iv disease, metastatic to 1 of the following sites: * skin, subcutaneous tissues, or distant lymph nodes * lung * other visceral sites with lactic dehydrogenase ≤ 2 times upper limit of normal (unless due to liver stasis) * de novo metastatic disease allowed provided patient refused any standard or approved stage-appropriate therapy for melanoma * measurable disease * hla-a2.1 positive (hla-a\*0201 by molecular subtyping) * mart-1-expressing tumor by reverse transcription polymerase chain reaction or immunohistochemistry * no symptomatic brain metastases and/or progression of cns metastases within the past 4 weeks * age 18 and over * performance status ecog 0-1 or * karnofsky 70-100% * hiv negative * negative pregnancy test * fertile patients must use effective barrier contraception during and for 3 months after study participation * more than 30 days since prior immunotherapy for metastatic, relapsed, or primary melanoma * more than 30 days since prior chemotherapy for metastatic, relapsed, or primary melanoma * more than 4 weeks since prior corticosteroids * more than 30 days since prior radiotherapy for metastatic, relapsed, or primary melanoma * more than 30 days since prior surgery for metastatic, relapsed, or primary melanoma. * more than 30 days since other prior therapy for metastatic, relapsed, or primary melanoma * more than 14 days since prior anti-infective therapy * more than 4 weeks since prior immune suppressive therapy (e.g., cyclosporine) exclusion criteria: * chronic hepatitis b or c * asthma * inflammatory bowel disease * celiac disease * history of chronic colitis or other chronic gastrointestinal conditions associated with diarrhea or bleeding * active chronic inflammatory or autoimmune disease, including any of the following: * psoriasis * rheumatoid arthritis * multiple sclerosis * hashimoto's thyroiditis * addison's disease * graves' disease * systemic lupus erythematosus * active infection or fever over 100° f within the past 3 days * allergy to study drugs * pregnant * symptomatic seizures * other medical problem that would preclude study participation * prior melanoma immunotherapy containing mart-1 antigen * prior anti-t-cell therapy * prior anti-cytotoxic t-lymphocyte-associated antigen-4 monoclonal antibody (cp-675,206) * organ allografts requiring long-term immune suppressive therapy

Keywords: recurrent melanoma stage iii melanoma stage iv melanoma